A Study Evaluating Efficacy and Safety of Multiple Treatment Combinations in Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck (Morpheus-Head and Neck Cancer)

About

Brief Summary

This is a Phase Ib/II, open-label, multicenter, randomized, umbrella study in participants with locally advanced squamous cell carcinoma of the head and neck (SCCHN). The study will enroll treatment-naive participants with resectable Stage III-IVA human papillomavirus (HPV)-negative, programmed death-ligand 1 (PD-L1)-positive SCCHN with measurable disease, as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) who have not received systemic treatment for their disease.

Primary Purpose

Treatment

Study Type

Interventional

Phase

Phase I/II

Eligibility

Gender

All

Healthy Volunteers

Minimum Age

18 Years

Maximum Age

N/A

Inclusion Criteria:

Eastern Cooperative Oncology Group Performance Status of 0 or 1
Histologically confirmed, resectable Stage III-IVA SCCHN
Eligible candidate for R0 resection with curative intent at the time of screening
HPV-negative test for oropharyngeal carcinoma, as determined locally by p16 immunohistochemistry (IHC), in situ hybridization, or polymerase chain reaction-based assay
Measurable disease (at least one target lesion), as assessed according to RECIST v1.1
PD-L1 expression, defined as a combined positive score (CPS) >= 1
Adequate hematologic and end-organ function
Negative HIV test with the following exception: patients with a positive HIV test at screening are eligible provided they are stable on anti-retroviral therapy, have a CD4 count >= 200/μL, and have an undetectable viral load.
Negative hepatitis B surface antibody (HBsAb) and negative total hepatitis B core antibody (HBcAb) test, negative hepatitis C virus (HCV) at screening

Exclusion Criteria:

HPV-positive oropharyngeal cancer, as determined locally by p16 IHC, in situ hybridization, or by polymerase chain reactions-based assay
Distantly metastasized SCCHN
Any prior therapy for SCCHN, including immunotherapy, chemotherapy, or RT
Prior treatment with any of the protocol-specified study treatments
Treatment with investigational therapy within 42 days prior to initiation of study treatment
Treatment with systemic immunostimulatory agents within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to initiation of study treatment
Prior allogeneic stem cell or solid organ transplantation
Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment
Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during study treatment or within 5 months after the final dose of study treatment
Active or history of autoimmune disease or immune deficiency
History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT scan)
History of malignancy other than SCCHN within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5 -year OS rate>90%)
Active tuberculosis
Severe infection within 4 weeks prior to initiation of study treatment
Treatment with therapeutic or prophylactic oral or intravenous (IV) antibiotics within 2 weeks prior to initiation of study treatment
Significant cardiovascular disease such a New York Heart Association cardiac disease (Class II or greater), myocardial infarction or cerebrovascular accident within 3 months prior to initiation of study treatment, unstable arrhytmia, or unstable angina
Major surgical procedure, other than for diagnosis, within 4 weeks prior to study initiation of study treatment, or anticipation of need for a major surgical procedure other than tumor resection, during the study
Any of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of investigational drug, may affect the interpretation of the results, impair the ability of the patient to participate in the study, or renders the patient at high risk form treatment complications
History of severe allergic reactions to chimeric or humanized antibodies or fusion proteins
Known hypersensitivity to Chinese hamster ovary cell products or recombinant human antibodies
Known allergy or hypersensitivity to any of the study drugs or their excipients
Known intolerance to any of the drugs required for premedication
Pregnancy or breastfeeding, or intention of becoming pregnant during the study
Eligible only for the control arm
Active EBV infection or known or suspected chronic EBV infection at screening

Specific Exclusion Criteria for Atezo+Tira+CP:

Known severe allergy or hypersensitivity to placlitaxel, platinum or platinum-containing compounds
Known history of severe hypersensitivity to products containing Cremophor EL
Creatinine clearance <45m./min (Calculated using the Cockcroft-Gault formula)

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